title: Interactions between tenofovir and nevirapine in CD4+ T cells and monocyte-derived macrophages restrict their intracellular accumulation.
abstract: OBJECTIVE
  There is no pharmacokinetic interaction between tenofovir and nevirapine, but a higher emergence rate of resistance mutations has been reported when these drugs are coadministered. We sought to examine if there is a potential intracellular interaction that may account for the emergence of resistant virus.
  
  
  METHODS
  Primary CD4+ and CD14+ cells were isolated from healthy volunteer blood. Monocyte-derived macrophages were differentiated from CD14+ cells. Accumulation of radiolabelled tenofovir and nevirapine was then assessed in these cells.
  
  
  RESULTS
  We show here that tenofovir and nevirapine immune cell intracellular concentrations are lower when coincubated in CD4+ cells and monocyte-derived macrophages, but not in CD14+ cells.
  
  
  CONCLUSIONS
  These data indicate a potential intracellular drug-drug interaction between these drugs that warrants further investigation.
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Liptrott
authors.forename: P
authors.initials: P
authors.lastname: Curley
authors.forename: D
authors.initials: D
authors.lastname: Moss
authors.forename: D J
authors.initials: DJ
authors.lastname: Back
authors.forename: S H
authors.initials: SH
authors.lastname: Khoo
authors.forename: A
authors.initials: A
authors.lastname: Owen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D019829:Nevirapine / Q000493:pharmacokinetics*; D063065:Organophosphonates / Q000493:pharmacokinetics*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine
keywords: HIV; drug–drug interactions; influx drug transporters